Iron Pathophysiology in Alzheimer’s Diseases

Abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Increasing evidence suggests that disorders of metal ion metabolism in the brain are one of the risk factors for the pathogenesis of AD. Iron, one of the endogenous metal ions, involves in many important physiological activities in the brain. Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, lactoferrin. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, leads to cell death, and ultimately influences the process of β-amyloid (Aβ) misfolding and plaque aggregation. Although the results are different, in general, iron has deposition in different brain regions of AD patients, which may impair normal cognitive function and behavior. Therefore, neuroimaging changes have so far been largely attributed to focal iron deposition accompanying the plaques at preclinical stages of AD, and iron-targeted therapeutic strategies have become a new direction. Iron chelators have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Future research will also focus on iron as an opportunity to study the mechanism of the occurrence and development of AD from the iron steady state to more fully clarify the etiology and prevention strategies.